Nicotine powder inhaler

ABSTRACT

This disclosure relates to nicotine powder inhalers where the nicotine powder is delivered at air flow rates that mimic a smoking regime.

This application is a continuation of U.S. application Ser. No.15/124,562, filed 8 Sep. 2016, which is a § 371 U.S. National Stage ofInternational Application No. PCT/IB2015/000924, filed 23 Apr. 2015,which claims the benefit of U.S. Provisional Application No. 61/984,967,filed 28 Apr. 2014 and EP Application No. 14166205.6, filed 28 Apr.2014, each of which are incorporated by reference herein.

This disclosure relates to nicotine powder inhalers, where the nicotinepowder is delivered at low air flow rates.

Dry powder inhalers (DPI) are known and are used to treat respiratorydiseases by delivering a dry powder comprising a pharmaceutical, inaerosol form through inhalation to the patients' airways. For deliverydeep into the lungs, particles in the range of 1 to 5 micrometers arerequired. In pharmaceutical dry powders, the active pharmaceuticalingredient (API) is agglomerated on the surface of larger carrierparticles, e.g. lactose, and DPI's therefore operate complex mechanismsto ensure such agglomerates disperse, break up or disaggregate beforethe API can be inhaled deep into the lungs. Pharmaceutical dry powderscontaining lactose as a carrier are typically in the range of 20 to 100micrometers. Existing DPI's for example first “grind” or de-agglomeratethe dry powder or impact the larger particles of the dry powder toresult in the aforementioned particle size range.

DPI's rely on the force of the patients' inhalation to entrain thepowder from the device to subsequently break-up the powder intoparticles that are small enough to enter the lungs. Sufficiently highinhalation rates are required to ascertain correct dosing and completedisaggregation of the powder. Typically a large amount of API remainsattached on the surface of the carrier and is deposited in the upperairways due to incomplete de-aggregation of the powder. Inhalation ratesof existing DPI's are usually in the range of 40-120 liters/min (L/min).Existing DPI's are therefore only suitable for delivering dry powders tousers in a manner that is different from the inhalation rate associatedwith smoking articles.

It would be desirable to provide a nicotine powder inhaler that candeliver nicotine powder to a user at inhalation or air flow rates thatare close to or within conventional smoking regime inhalation or airflow rates. It would be desirable to provide a nicotine powder inhalerthat is a similar size and configuration as a conventional cigarette. Itwould be desirable to provide a nicotine powder inhaler that can providea metered dose of nicotine and an optional simultaneous delivery of asecond active ingredient.

Nicotine powder inhalers of the invention described herein can beutilized to deliver nicotine to a user at inhalation or air flow ratesthat are within conventional smoking regime inhalation or air flowrates. The nicotine powder inhalers can provide a predictable andmetered dose of nicotine or other optional active ingredients. Nicotinepowder inhalers of the invention described herein have a similar sizeand configuration as a conventional cigarette and have a simpleconfiguration.

As described herein, a nicotine powder inhaler includes a body extendingbetween a mouthpiece and a distal end portion and an airflow channelextends along the body of the inhaler. A nicotine powder receptaclealong the airflow channel holds a dose of nicotine powder. The dose ofnicotine powder can be inhaled into lungs of a user at an inhalationrate of less than about 5 L/min or preferable less than about 2 L/min.Preferably the dose of nicotine powder can be contained in a capsulethat can be pierced by the inhaler. Preferably the dose of nicotine is anicotine salt.

Various aspects of the nicotine powder inhalers described herein mayhave one or more advantages relative to standard dry powder inhalers.For example, the nicotine powder inhalers deliver the dry powdernicotine at inhalation or air flow rates that are within conventionalsmoking regime inhalation or air flow rates and inhalation manner. Thisallows users with even compromised or impaired breathing conditions tosuccessfully deliver the dry powder nicotine and optional second activeingredients. The nicotine powder inhalers described herein have asimplified configuration that allows the user to predetermine themetered dose of dry powder nicotine and optional second activeingredients. The dry powder nicotine utilized with this inhaler, anddescribed herein, is carrier-free and has a constant size from storageto inhalation. Additional advantages of one or more aspects flavourdelivery system described herein will be evident to those of skill inthe art upon reading and understanding the present disclosure.

The term “nicotine” refers to nicotine and nicotine derivatives such asnicotine salts.

The present disclosure provides nicotine powder inhalers for inhalingdry powder nicotine. The nicotine powder inhalers include a bodyextending between a mouthpiece portion and a distal end portion. Anairflow channel extends between the mouthpiece portion and a distal endportion and a nicotine powder receptacle. The nicotine powder receptacleis disposed along the airflow channel and is configured to receive adose of nicotine powder. Surprisingly, the dose of nicotine powder canbe inhaled into lungs of a user at an inhalation rate of less than about5 L/min or less than about 2 L/min which mimics the inhalation flow rateutilized for a conventional smoking regime. The nicotine powder inhalersdescribed herein are “passive” devices that utilize only the inhalationair flow created by the lungs of a user to create air flow though thebody of the nicotine powder inhaler.

The airflow path or airflow channel through the body of the inhaler is asimple path or channel. In many embodiments the airflow path or airflowchannel through the body of the inhaler is parallel to a longitudinalaxis of the inhaler and is linearly extending along an entire length ofthe inhaler body. In some embodiments the inhaler includes two or threeco-extensive airflow channels. One, two or all three of the airflowchannels can include a capsule receptacle. In some embodiments the oneor more airflow paths or airflow channels includes a swirl generatorelement that is configured to induce a rotational movement of theairflow moving through the body of the inhaler. The swirl generatorelement can discharge into an outlet channel that can be a larger volumethan the one or more individual airflow paths or airflow channels.

The nicotine powder receptacle can receive a capsule of nicotine powder.The capsule can contain a predetermined amount or dose of nicotinepowder. In many embodiments the capsule can contain enough nicotinepowder to provide at least 2 inhalations or “puffs” of nicotine powder,or at least about 5 inhalations or “puffs” of nicotine powder, or atleast about 10 inhalations or “puffs” of nicotine powder. In manyembodiments the capsule can contain enough nicotine powder to providefrom about 5 to 50 inhalations or “puffs” of nicotine powder, or fromabout 10 to 30 inhalations or “puffs” of nicotine powder. Eachinhalation or “puff” of nicotine powder can deliver from about 0.5 mg toabout 3 mg of nicotine powder to the lungs of the user or from about 1mg to about 2 mg of nicotine powder to the lungs of the user or about 1mg of nicotine powder to the lungs of the user.

In many embodiments the capsule holds or contains at least about 5 mg ofnicotine powder or at least about 10 mg of nicotine powder. In manyembodiments the capsule holds or contains less than about 30 mg ofnicotine powder or less than about 25 mg of nicotine powder, or lessthan 20 mg of nicotine powder. In many embodiments the capsule holds orcontains from about 5 mg to about 30 mg of nicotine powder or from about10 mg to about 20 mg of nicotine powder.

The capsule can be formed of an airtight material that can be pierced orpunctured by the inhaler. The capsule can formed of a metallic orpolymeric material that serves to keep contaminates out of the capsulebut can be pierced or punctured by the inhaler during use.

The inhaler can include a piercing element or pair of opposing piercingelements that are configured to pierce the capsule of nicotine powder.The piercing element or pair of opposing piercing elements fluidlyconnect the airflow channel with the dose of nicotine powder. Thepiercing element or pair of opposing piercing elements can engage withthe capsule of nicotine powder upon loading the capsule of nicotinepowder into the nicotine powder receptacle or upon demand by an actuatoron the body of the inhaler.

In many embodiments the nicotine powder is a pharmaceutically acceptablenicotine salt or nicotine salt hydrate. Useful nicotine salts ornicotine salt hydrates include nicotine bitartrate, nicotine salicylate,nicotine fumarate, nicotine mono-pyruvate, nicotine glutamate ornicotine hydrochloride, for example. The compound combining withnicotine to from the salt or salt hydrate can be chosen based on itspharmacological effect. For example: nicotine salicylate can beadministered for fever relief, as an anti-inflammatory or painkiller;nicotine fumarate can be administered to treat multiple sclerosis; andnicotine mono-pyruvate can be administered for treating chronicobstructive pulmonary disease (COPD) or for weight loss.

The nicotine powder can have any useful size distribution for inhalationdelivery into the lungs of a user. In many embodiments at least about 90wt % of the nicotine powder has a particle size of about 10 micrometersor less, preferably about 7 micrometers or less. The nicotine powderpreferably has a mean average diameter size range from about 0.1 toabout 10 micrometers, more preferably from about 1 to about 7micrometers, even more preferably from about 2 to 6 about micrometers.

Conventional formulations for dry powder inhalation typically containcarrier particles that serve to increase the fluidization of the activeparticles since the active particles are typically too small to beinfluenced by the airflow though the inhaler. The carrier particles thuswere utilized to improve the dose uniformity by acting as a diluent orbulking agent in a formulation. However, the nicotine powder describedherein is carrier-free. Being carrier-free allows the nicotine powder tobe inhaled and delivered to the user's lungs at inhalation or airflowrates that are similar to typical smoking regime inhalation or airflowrates. In addition, since the nicotine powder is carrier-free, theairflow path of the inhaler can have simple geometry or a simpleconfiguration.

The carrier-free nicotine powder described herein can be a surfacemodified nicotine salt where the nicotine salt particle is a coatedparticle. One preferred coating material is L-leucine. Thesecarrier-free nicotine powders are described and are available fromTeicos Pharma Inc., Espoo, Finland. One particularly useful nicotinepowder is an L-luecine coated nicotine bitartrate.

A second active agent or ingredient can be delivered along with thenicotine powder. The second active agent or ingredient can be mixed withthe nicotine in the capsule or separate from the nicotine in its owncapsule. The second active agent or ingredient can be fluidized with thenicotine powder and inhaled by a user.

This second active agent or ingredient can be any active pharmaceuticalmaterial. In many embodiments the second active agent or ingredient canbe combined with the nicotine powder described herein by blending thetwo materials during inhalation. The nicotine powder and the secondactive agent or ingredient can be blended in the same capsule orprovided in series in a single air flow channel in the DPI or providedin parallel in separate flow channels of the DPI. The second activeagent or ingredient can have a similar mean average diameter size rangeas the nicotine powder described above.

The nicotine powder inhaler is less complex and has a simplified powderstorage and airflow path as compared to existing DPIs, and does not needa carrier ingredient, such as lactose, as described above. Therefore thecomplex mechanisms to dissociate/disaggregate a pharmaceutical drypowder is not required in the described nicotine inhaler and thereforethe described nicotine inhaler operates under low airflow. The inhalerdoes not require the typical high inhalation rates of conventional DPIsto deliver the dry nicotine powders described above deep into the lungs.

The nicotine inhaler according to this invention operates using a flowrate of less than about 5 L/min or less than about 3 L/min or less thanabout 2 L/min or about 1.6 L/min. In many embodiments the flow rate isin a range from about 1 L/min to about 3 L/min or from about 1.5 L/minto about 2.5 L/min. In preferred embodiments the inhalation rate or flowrate is similar to that of Health Canada smoking regime, that is about1.6 L/min. In contrast, a conventional DPI operates at a flow rate ofabout 40-120 L/min and often requires an energy source or propellant topromote air flow to achieve this air flow rate.

The nicotine inhaler described herein can be used by a consumer likesmoking a conventional cigarette or vaping an electronic cigarette. Suchsmoking or vaping is characterized by two steps: a first step duringwhich a small volume containing the full amount of nicotine desired bythe consumer is drawn into the mouth cavity, followed by a second stepduring which this small volume comprising the aerosol comprising thedesired amount of nicotine is further diluted by fresh air and drawndeeper into the lungs. Both steps are controlled by the consumer. Duringthe first inhalation step the consumer can determine the amount ofnicotine to be inhaled. During the second step, the consumer candetermine the volume for diluting the first volume to be drawn deeperinto the lungs, maximizing the concentration of active agent deliveredto the airway epithelial surface. This smoking mechanism is sometimescalled “puff-inhale-exhale”.

All scientific and technical terms used herein have meanings commonlyused in the art unless otherwise specified. The definitions providedherein are to facilitate understanding of certain terms used frequentlyherein.

The terms “upstream” and “downstream” refer to relative positions ofelements of the inhaler described in relation to the direction ofinhalation air flow as it is drawn through the body of the inhaler froma distal end portion to the mouthpiece portion.

As used herein, the singular forms “a”, “an”, and “the” encompassembodiments having plural referents, unless the content clearly dictatesotherwise.

As used herein, “or” is generally employed in its sense including“and/or” unless the content clearly dictates otherwise. The term“and/or” means one or all of the listed elements or a combination of anytwo or more of the listed elements.

As used herein, “have”, “having”, “include”, “including”, “comprise”,“comprising” or the like are used in their open ended sense, andgenerally mean “including, but not limited to”. It will be understoodthat “consisting essentially of”, “consisting of”, and the like aresubsumed in “comprising,” and the like.

The words “preferred” and “preferably” refer to embodiments of theinvention that may afford certain benefits, under certain circumstances.However, other embodiments may also be preferred, under the same orother circumstances. Furthermore, the recitation of one or morepreferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the disclosure, including the claims.

FIGS. 1-7 are schematic diagrams of illustrative nicotine powderinhalers 10. FIGS. 3-7 are shown with transparent bodies for ease ofillustration of the flow channels and internal elements. The schematicdrawings are not necessarily to scale and are presented for purposes ofillustration and not limitation. The drawings depict one or more aspectsdescribed in this disclosure. However, it will be understood that otheraspects not depicted in the drawing fall within the scope and spirit ofthis disclosure.

Referring now to FIG. 1 and FIG. 2 , the nicotine powder inhalers 10include a mouthpiece portion 12 and a distal end portion 14 and anicotine capsule 20 disposed between them. Piercing elements 11A and 11Bare configured to pierce the capsule 20 and fluidly connect the airflowchannel 13 of the mouthpiece portion 12 with the airflow channel 15 ofthe distal end portion 14. The airflow channel extends linearly along alength of the nicotine powder inhaler 10. FIG. 2 further illustrates thecapsule 20 within a receptacle 25 that can be re-usable.

FIG. 3 and FIG. 4 illustrate nicotine powder inhalers 10 having a singlelinear airflow channel 13, 15. Piercing elements 11A and 11B extend intoa nicotine powder receptacle 30 and are configured to pierce thenicotine powder capsule and fluidly connect the airflow channel 13 ofthe mouthpiece portion 12 with the airflow channel 15 of the distal endportion 14. The airflow channel extends linearly along a length of thenicotine powder inhaler 10 from a proximal mouthpiece end 18 to a distalend 19. The mouthpiece portion 12 can connect with the distal endportion 14 via a bayonet-type connection. In FIG. 3 the mouthpieceportion 12 is not symmetrical with the distal end portion 14. In In FIG.4 the mouthpiece portion 12 is symmetrical with the distal end portion14.

FIG. 5 and FIG. 6 is a further illustrative nicotine powder inhaler 10.FIG. 6 is a view of FIG. 5 taken along lines 6-6. This embodimentincludes three airflow channels 15 and a first, second and third powderreceptacles 30, 32 and 33 respectively. A nicotine powder capsule can bereceived in at least one of the powder receptacles 30, 32 and 33. Insome embodiments, a second active agent can be received in at least oneof the powder receptacles 30, 32 and 33. The three flow channels 15fluidly connect to an outlet channel 40 via a swirl generator 50configured to induce rotation movement in the airflow. The airflowchannels 15 extend linearly along a length of the nicotine powderinhaler 10 from a proximal mouthpiece end 18 to a distal end 19. Aventilation element 70 can be disposed along an airflow channels 15 toprovide dilution air, as desired.

FIG. 7 is a further illustrative nicotine powder inhaler 10. Thisembodiment includes three airflow channels 15A, 15B and 15C and first,second and third powder receptacles 30, 32 and 33 respectively. Anicotine powder capsule can be received in at least one of the powderreceptacles 30, 32 and 33. In some embodiments, a second active agentcan be received in at least one of the powder receptacles 30, 32 and 33.The three flow channels 15 fluidly connect to an outlet channel 40 via aswirl generator 50 configured to induce rotation movement in theairflow. The airflow channels 15A, 15B extend linearly along a length ofthe nicotine powder inhaler 10 from a proximal mouthpiece end 18 to adistal end 19. In some embodiments an airflow loop element 60 isdisposed along an airflow channels 15C.

The invention claimed is:
 1. A powder inhaler comprising: a bodyextending between a proximal mouthpiece end and a distal end, theproximal mouthpiece end comprising an outlet; a swirl generator elementdisposed in the body and constructed to induce rotational movement inthe airflow moving through the body; an airflow channel extending alongthe body, the airflow channel comprising a plurality of inlet channelsextending to the swirl generator and an outlet airflow channel extendingparallel to a longitudinal axis of the body from the swirl generator tothe outlet at the proximal mouthpiece end; and a nicotine powderreceptacle disposed along the airflow channel, the swirl generatordisposed adjacent to the nicotine powder receptacle; wherein the inhaleris constructed to deliver a dose of powder via air flow created byinhalation at the proximal mouthpiece end at an inhalation rate of lessthan about 5 L/min.
 2. A powder inhaler according to claim 1, whereinthe outlet channel has a volume being greater than a volume of theairflow channel.
 3. A powder inhaler according to claim 1, wherein theairflow channel comprises three inlet channels.
 4. A powder inhaleraccording to claim 1, comprising a cylindrical mouthpiece portion.
 5. Apowder inhaler according to claim 1, wherein the receptacle defines acylindrical shape.
 6. A powder inhaler according to claim 1, wherein thebody has a transverse cross-section shape having a major axis and aminor axis, and the major axis is longer than the minor axis.
 7. Asystem for providing powder, the system comprising the powder inhaler ofclaim 1 and further comprising a capsule containing nicotine powderwithin the nicotine powder receptacle.
 8. The system of claim 7, whereinthe capsule further comprises a flavourant powder.
 9. The system ofclaim 7, wherein the capsule further comprises an active agent.
 10. Thesystem of claim 7, wherein the powder has a mean average particle sizein a range from 1 micrometer to 7 micrometers.
 11. The system of claim10, wherein at least 90% of the powder has a particle size of 7micrometers or less.
 12. The system of claim 7, wherein the powdercomprises L-Leucine.
 13. The system of claim 7, wherein the nicotinepowder comprises nicotine bitartrate.
 14. The system of claim 7, whereinthe nicotine powder comprises nicotine glutamate.
 15. The system ofclaim 7, wherein powder comprises an amount of powder sufficient todeliver from 10 to 30 inhalations of powder.
 16. A method of inhalingpowder into lungs of a user: inhaling air through the system of claim 7at a flow rate of less than about 2 L/min to deliver powder into lungsof a user.
 17. The method of claim 16, wherein the inhaling air throughthe system induces rotational movement of air flowing through the powderinhaler.
 18. The method of claim 16, wherein the inhaling air throughthe system induces rotational movement of air flowing through the powderinhaler and delivers nicotine powder and flavourant powder into lungs ofa user.
 19. The system of claim 1, wherein the plurality of inletchannels extends from the distal end to the swirl generator element.